Adoptive cell therapy for advanced melanoma patients

A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients

This study is testing a new cell therapy for patients with advanced melanoma to see if it can help them when other treatments haven't worked.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sheba Medical Center (other gov)
• Drugs / interventions: chemotherapy, Nivolumab, Ipilimumab, Cyclophosphamide, Fludarabine
• Locations: 1 site (Ramat Gan)
• Trial ID: NCT03166397 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma. The approach involves a reduced-intensity, non-myeloablative lymphodepleting regimen followed by high-dose interleukin-2 (IL-2) administration. Additionally, two new treatment arms are included: one combining TIL-ACT with Nivolumab and another with fecal microbiota transplantation (FMT) and Ipilimumab. The study aims to evaluate the safety and efficacy of these combinations in patients who have not responded to standard treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with measurable, refractory metastatic melanoma and specific eligibility criteria.

Not a fit: Patients with melanoma that is not measurable or those who have not been treated for brain metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve treatment outcomes for patients with advanced melanoma.

How similar studies have performed: Previous studies have shown promising results with adoptive cell therapy approaches, indicating potential for success in this novel combination treatment.

Eligibility criteria

Inclusion Criteria:

1. Measurable metastatic Melanoma with at least one lesion that is resectable for TIL generation.
2. Refractory to standard treatment
3. Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 6 weeks.
4. Greater than or equal to 18 years of age.
5. Willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
6. Clinical performance status of ECOG 0 or 1
7. Hematology:

   Absolute neutrophil count greater than 1000/mm3 without support of filgrastim Normal WBC (greater than 3000/mm3). Hemoglobin greater than 8.0 g/dL Platelet count greater than 100,000/mm3
8. Serology:

   Seronegative for HIV antibody. Seronegative for Hepatitis B or Hepatitis C.
9. Chemistry:

   Serum ALT/AST less than three times the upper limit of normal (ULN). Serum creatinine less than or equal to 1.6 mg/dL Total bilirubin no more than 1.5 times the ULN, except in patients with Gilbert Syndrome who must have a total bilirubin less than 3 mg/dL.
10. Negative pregnancy test in women of child bearing potential because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
11. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.

Exclusion Criteria:

1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant.
2. Systemic steroid therapy required.
3. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
5. Opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
6. History of severe immediate hypersensitivity reaction to any of the agents used in this study , including history of an anaphylactic reaction to penicillin or gentamicin
7. History of coronary revascularization or ischemic symptoms
8. Any patient known to have an LVEF less than or equal to 50 percent .
9. Documented LVEF of less than or equal to 50 percent tested in patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
10. Documented FEV1 and DLCO (relative to predicted) less than or equal to 60 percent

Where this trial is running

Ramat Gan

• Sheba Medical Center — Ramat Gan, Israel (RECRUITING)

Study contacts

• Study coordinator: Meital Bar

Conditions: Malignant Melanoma Stage IV